2. Academic Validation
  3. Mannose-modified multifunctional iron-based nanozyme for hepatocellular carcinoma treatment by remodeling the tumor microenvironment

Mannose-modified multifunctional iron-based nanozyme for hepatocellular carcinoma treatment by remodeling the tumor microenvironment

  • Colloids Surf B Biointerfaces. 2025 Feb 3:250:114548. doi: 10.1016/j.colsurfb.2025.114548.
Qi Liu 1,  Ziwei Liang 2,  Jiapu Wang 1,  Yuhui Wang 1,  Jie Wang 1,  Shaojie Wang 1,  Zhi Du 3,  Liqin Zhao 3,  Yan Wei 4,  Di Huang 5
Affiliations

Affiliations

  • 1 Department of Biomedical Engineering, Research Center for Nano-biomaterials & Regenerative Medicine, College of Artificial Intelligence, Shanxi Key Laboratory of Materials Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China.
  • 2 Department of Biomedical Engineering, Research Center for Nano-biomaterials & Regenerative Medicine, College of Artificial Intelligence, Shanxi Key Laboratory of Materials Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China; NHC Key Laboratory of Glycoconjuates Research Department of Biochemistry and Molecular, Biology School of Basic Medical Sciences, Fudan University, Shanghai 200032, China; Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering, Taiyuan 030032, China; Shanxi Provincial Key Laboratory for Functional Proteins, Shanxi Jinbo Bio-Pharmaceutical Co., Ltd, Taiyuan 030032, China. Electronic address: liangziweiguozhong@163.com.
  • 3 Department of Biomedical Engineering, Research Center for Nano-biomaterials & Regenerative Medicine, College of Artificial Intelligence, Shanxi Key Laboratory of Materials Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China; Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering, Taiyuan 030032, China.
  • 4 Department of Biomedical Engineering, Research Center for Nano-biomaterials & Regenerative Medicine, College of Artificial Intelligence, Shanxi Key Laboratory of Materials Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China; Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering, Taiyuan 030032, China; Shanxi Provincial Key Laboratory for Functional Proteins, Shanxi Jinbo Bio-Pharmaceutical Co., Ltd, Taiyuan 030032, China. Electronic address: weiyanbme@gmail.com.
  • 5 Department of Biomedical Engineering, Research Center for Nano-biomaterials & Regenerative Medicine, College of Artificial Intelligence, Shanxi Key Laboratory of Materials Strength & Structural Impact, Taiyuan University of Technology, Taiyuan 030024, China; Shanxi-Zheda Institute of Advanced Materials and Chemical Engineering, Taiyuan 030032, China; Shanxi Provincial Key Laboratory for Functional Proteins, Shanxi Jinbo Bio-Pharmaceutical Co., Ltd, Taiyuan 030032, China. Electronic address: huangjw2067@163.com.
PMID: 39923382 DOI: 10.1016/j.colsurfb.2025.114548
Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, with conventional treatments often accompanied by severe side effects. Recently, nanozymes have been extensively employed in Cancer therapy due to their enhanced enzymatic activities, stability compared to native Enzymes. However, a standalone nanozyme exhibits insufficient targeting capability and fails to specifically localize to the pathological site. In this study, we successfully synthesized a multifunctional iron-based-nanozyme delivery system - Fe3O4-OA-DHCA-PEI-MAN@DSF modified with PEI and MAN by the thermal decomposition method. This mannose-modified nanozyme can specifically target HCC cells via an external magnetic field and mannose-mannose receptor (MRC2) binding. In addition, it exhibits good biocompatibility and pH-dependent drug release characteristics. Within the acidic tumor microenvironment, the iron-based nanozyme initiates intracellular fenton reactions, boosting Reactive Oxygen Species (ROS) production, which ultimately induces Apoptosis in HCC cells. Concurrently, the disulfiram small molecule released from the Fe3O4-OA-DHCA-PEI-MAN@DSF nanozyme binds to the FROUNT factor within monocyte-macrophages, thereby inhibiting their response to chemotactic signals emitted by liver Cancer cells. This process ultimately suppresses the recruitment of macrophages by HCC cells, reshaping the tumor microenvironment and supporting effective liver Cancer treatment. Moreover, this nanozyme system holds potential for MRI-guided targeted chemotherapy combined with chemodynamic therapy, aiming to refine the early diagnosis and precision treatment of hepatic carcinoma, and paving the way for the creation of sophisticated integrated nanoplatforms melding diagnostic and therapeutic functionalities.

Keywords

Fe(3)O(4); Hepatocellular carcinoma; Mannose; Nanozymes; Tumor Microenvironment remodeling.

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